3D spheroid culture enhances survival and therapeutic capacities of MSCs injected into ischemic kidney

• Published in: Journal of cellular and molecular medicine Vol. 20; no. 7; pp. 1203 - 1213
• Main Authors: Xu, Yong, Shi, Taoping, Xu, Axiang, Zhang, Lei
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.07.2016
• Subjects: acute kidney injury; Acute Kidney Injury - pathology; Acute Kidney Injury - physiopathology; Acute Kidney Injury - therapy; Adipose Tissue - cytology; Animals; Antioxidants - metabolism; Apoptosis - drug effects; Cell Culture Techniques - methods; Cell Separation; Cell Survival - drug effects; Extracellular Matrix Proteins - secretion; Humans; Hydrogen Peroxide - pharmacology; Ischemia - pathology; Ischemia - physiopathology; Ischemia - therapy; Kidney - blood supply; Kidney - drug effects; Kidney - pathology; Kidney - physiopathology; Kidney Function Tests; Male; Mesenchymal Stem Cell Transplantation; mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Neovascularization, Physiologic - drug effects; Original; Paracrine Communication - drug effects; paracrine secretion; Rats, Sprague-Dawley; Spheroids, Cellular - cytology; three‐dimensional culture; three-dimensional culture; paracrine secretion; acute kidney injury; mesenchymal stem cells
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.12651

Three‐dimensional (3D) cell culture has been reported to increase the therapeutic potentials of mesenchymal stem cells (MSCs). In this study, we aimed to investigate the therapeutic effects of 3D spheroids of human adipose‐derived MSCs for acute kidney injury (AKI). In vitro studies indicated that 3D spheroids of MSCs produced higher levels of extracellular matrix proteins (including collagen I, fibronectin and laminin), and exhibited stronger anti‐apoptotic and anti‐oxidative capacities than two‐dimensional (2D) cultured cells. Furthermore, 3D culture increased the paracrine secretion of cytokines by MSCs, including angiogenic factors (VEGF and basic fibroblast growth factor), anti‐apoptotic factors (epidermal growth factor and hepatocyte growth factor), the anti‐oxidative factor insulin‐like growth factor and the anti‐inflammatory protein tumour necrosis factor‐alpha stimulated gene/protein 6. Consistent with in vitro experiments, 3D spheroids of MSCs showed enhanced survival and paracrine effects in vivo. More importantly, when injected into the kidney of model rats with ischemia‐reperfusion (I/R)‐induced AKI, 3D spheroids were more beneficial in protecting the I/R kidney against apoptosis, reducing tissue damage, promoting vascularization and ameliorating renal function compared with 2D cultured cells. Therefore, the 3D culture strategy improved the therapeutic effects of MSCs, and might be promising for AKI treatment.